Respiratory Motion Guided Four Dimensional Cone Beam Computed Tomography: Encompassing Irregular Breathing

Four dimensional cone beam computed tomography (4DCBCT) images su er from angular under sampling and bunching of projections due to a lack of feedback between the respiratory signal and the acquisition system. To address this problem, Respiratory Motion Guided 4DCBCT (RMG-4DCBCT) regulates the gantry velocity and projection time interval, in response to the patient's respiratory signal, with the aim of acquiring evenly spaced projections in a number of phase or displacement bins during the respiratory cycle. Our previous study of RMG- 4DCBCT was limited to sinusoidal breathing traces. Here we expand on that work to provide a practical algorithm for the case of real patient breathing data. We give a complete description of RMG-4DCBCT including full details on how to implement the algorithms to determine when to move the gantry and when to acquire projections in response to the patient's respiratory signal. We simulate a realistic working RMG-4DCBCT system using 112 breathing traces from 24 lung cancer patients. Acquisition used phase-based binning and parameter settings typically used on commercial 4DCBCT systems (4 minute acquisition time, 1200 projections across 10 respiratory bins), with the acceleration and velocity constraints of current generation linear accelerators. We quanti ed streaking artefacts and image noise for conventional and RMG-4DCBCT methods by reconstructing projection data selected from an oversampled set of Catphan phantom projections. RMG-4DCBCT allows us to optimally trade-o image quality, acquisition time and image dose. For example, for the same image quality and acquisition time as conventional 4DCBCT approximately half the imaging dose is needed. Alternatively, for the same imaging dose, the image quality as measured by the signal to noise ratio, is improved by 63% on average. C- arm CBCT systems, with an acceleration up to 200 degrees=s2, a velocity up to 100 degrees=s and the acquisition of 80 projections per second, allow the image acquisition time to be reduced to below 60 seconds. We have made considerable progress towards realising a system to reduce projection clustering in conventional 4DCBCT imaging and hence reduce the imaging dose to the patient

The First Implementation of Respiratory Triggered 4DCBCT on a Linear Accelerator

Four Dimensional Cone Beam Computed Tomography (4DCBCT) is an image guidance strategy used for patient positioning in radiotherapy. In conventional implementations of 4DCBCT, a constant gantry speed and a constant projection pulse rate are used. Unfortunately, this leads to higher imaging doses than are necessary because a large number of redundant projections are acquired. In theoretical studies, we have previously demonstrated that by suppressing redundant projections the imaging dose can be reduced by 40-50% for a majority of patients with little reduction in image quality. The aim of this study was to experimentally realise the projection suppression technique, which we have called Respiratory Triggered 4DCBCT (RT-4DCBCT). A real-time control system was developed that takes the respiratory signal as input and computes whether to acquire, or suppress, the next projection trigger during 4DCBCT acquisition. The CIRS dynamic thorax phantom was programmed with a 2cm peak-to-peak motion and periods ranging from 2 to 8 seconds. Image quality was assessed by computing the edge response width of a 3cm imaging insert placed in the phantom as well as the signal to noise ratio of the phantoms tissue and the contrast to noise ratio between the phantoms lung and tissue. The standard deviation in the Superior-Inferior direction of the 3cm imaging insert was used to assess intra-phase bin displacement variations with a higher standard deviation implying more motion blur. The 4DCBCT imaging dose was reduced by 8.6%, 41%, 54%, 70% and 77% for patients with 2, 3, 4, 6 and 8 second breathing periods respectively when compared to conventional 4DCBCT. The standard deviation of the intra-phase bin displacement variation of the 3cm imaging insert was reduced by between 13% and 43% indicating a more consistent position for the projections within respiratory phases. For the 4 second breathing period, the edge response width was reduced by 39% (0.8mm) with only a 6-7% decrease in the signal to noise and contrast to noise ratios. RT-4DCBCT has been experimentally realised and reduced to practice on a linear accelerator with a measurable imaging dose reductions over conventional 4DCBCT and little degradation in image quality

Measurement of gut permeability using fluorescent tracer agent technology

Abstract The healthy gut restricts macromolecular and bacterial movement across tight junctions, while increased intestinal permeability accompanies many intestinal disorders. Dual sugar absorption tests, which measure intestinal permeability in humans, present challenges. Therefore, we asked if enterally administered fluorescent tracers could ascertain mucosal integrity, because transcutaneous measurement of differentially absorbed molecules could enable specimen-free evaluation of permeability. We induced small bowel injury in rats using high- (15 mg/kg), intermediate- (10 mg/kg), and low- (5 mg/kg) dose indomethacin. Then, we compared urinary ratios of enterally administered fluorescent tracers MB-402 and MB-301 to urinary ratios of sugar tracers lactulose and rhamnose. We also tested the ability of transcutaneous sensors to measure the ratios of absorbed fluorophores. Urinary fluorophore and sugar ratios reflect gut injury in an indomethacin dose dependent manner. The fluorophores generated smooth curvilinear ratio trajectories with wide dynamic ranges. The more chaotic sugar ratios had narrower dynamic ranges. Fluorophore ratios measured through the skin distinguished indomethacin-challenged from same day control rats. Enterally administered fluorophores can identify intestinal injury in a rat model. Fluorophore ratios are measureable through the skin, obviating drawbacks of dual sugar absorption tests. Pending validation, this technology should be considered for human use

Coherent Pair Production by Photons in the 20-170 GeV Energy Range Incident on Crystals and Birefringence

The cross section for coherent pair production by linearly polarised photons in the 20-170 GeV energy range was measured for photon aligned incidence on ultra-high quality diamond and germanium crystals. The theoretical description of coherent bremsstrahlung and coherent pair production phenomena is an area of active theoretical debate and development. However, under our experimental conditions, the theory predicted the combined cross section and polarisation experimental observables very well indeed. In macroscopic terms, our experiment measured a birefringence effect in pair production in a crystal. This study of this effect also constituted a measurement of the energy dependent linear polarisation of photons produced by coherent bremsstrahlung in aligned crystals. New technologies for manipulating high energy photon beams can be realised based on an improved understanding of QED phenomena at these energies. In particular, this experiment demonstrates an efficient new polarimetry technique. The pair production measurements were done using two independent methods simultaneously. The more complex method using a magnet spectrometer showed that the simpler method using a multiplicity detector was also viable.Comment: 10 pages, 13 figures, 1 table, REVTeX4 two column, Version for publicatio

Linear to Circular Polarisation Conversion using Birefringent Properties of Aligned Crystals for Multi-GeV Photons

We present the first experimental results on the use of a thick aligned Si crystal acting as a quarter wave plate to induce a degree of circular polarisation in a high energy linearly polarised photon beam. The linearly polarised photon beam is produced from coherent bremsstrahlung radiation by 178 GeV unpolarised electrons incident on an aligned Si crystal, acting as a radiator. The linear polarisation of the photon beam is characterised by measuring the asymmetry in electron-positron pair production in a Ge crystal, for different crystal orientations. The Ge crystal therefore acts as an analyser. The birefringence phenomenon, which converts the linear polarisation to circular polarisation, is observed by letting the linearly polarised photons beam pass through a thick Si quarter wave plate crystal, and then measuring the asymmetry in electron-positron pair production again for a selection of relative angles between the crystallographic planes of the radiator, analyser and quarter wave plate. The systematics of the difference between the measured asymmetries with and without the quarter wave plate are predicted by theory to reveal an evolution in the Stokes parameters from which the appearance of a circularly polarised component in the photon beam can be demonstrated. The measured magnitude of the circularly polarised component was consistent with the theoretical predictions, and therefore is in indication of the existence of the birefringence effect.Comment: 12 pages, 12 figures, 1 table, REVTeX4 two column, Version for publicatio

Results on the Coherent Interaction of High Energy Electrons and Photons in Oriented Single Crystals

The CERN-NA-59 experiment examined a wide range of electromagnetic processes for multi-GeV electrons and photons interacting with oriented single crystals. The various types of crystals and their orientations were used for producing photon beams and for converting and measuring their polarisation. The radiation emitted by 178 GeV unpolarised electrons incident on a 1.5 cm thick Si crystal oriented in the Coherent Bremsstrahlung (CB) and the String-of-Strings (SOS) modes was used to obtain multi-GeV linearly polarised photon beams. A new crystal polarimetry technique was established for measuring the linear polarisation of the photon beam. The polarimeter is based on the dependence of the Coherent Pair Production (CPP) cross section in oriented single crystals on the direction of the photon polarisation with respect to the crystal plane. Both a 1 mm thick single crystal of Germanium and a 4 mm thick multi-tile set of synthetic Diamond crystals were used as analyzers of the linear polarisation. A birefringence phenomenon, the conversion of the linear polarisation of the photon beam into circular polarisation, was observed. This was achieved by letting the linearly polarised photon beam pass through a 10 cm thick Silicon single crystal that acted as a "quarter wave plate" (QWP) as suggested by N. Cabibbo et al.Comment: Presented at International workshop "Relativistic Channeling and Related Coherent Phenomena", Frascati (Rome) 23-26 March 200

Coherent bremsstrahlung, boherent pair production, birefringence and polarimetry in the 20-170 GeV energy range using aligned crystals

The processes of coherent bremsstrahlung (CB) and coherent pair production (CPP) based on aligned crystal targets have been studied in the energy range 20-170 GeV. The experimental arrangement allowed for measurements of single photon properties of these phenomena including their polarization dependences. This is significant as the theoretical description of CB and CPP is an area of active theoretical debate and development. With the theoretical approach used in this paper both the measured cross sections and polarization observables are predicted very well. This indicates a proper understanding of CB and CPP up to energies of 170 GeV. Birefringence in CPP on aligned crystals is applied to determine the polarization parameters in our measurements. New technologies for high energy photon beam optics including phase plates and polarimeters for linear and circular polarization are demonstrated in this experiment. Coherent bremsstrahlung for the strings-on-strings (SOS) orientation yields a larger enhancement for hard photons than CB for the channeling orientations of the crystal. Our measurements and our calculations indicate low photon polarizations for the high energy SOS photons.Comment: 23 pages, 27 figures, 2 tables, REVTeX4 two column

Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor.

Background and objectivesObesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis.Materials and methodsMale C57BL/6 J mice were fed a high-fat diet. Streptozotocin was injected into mice to induce diabetes. Experimental groups were injected with cathelicidin and CD36 overexpressing lentiviruses. Human mesenteric fat adipocytes, mouse 3T3-L1 differentiated adipocytes and human HepG2 hepatocytes were used in the in vitro experiments. Cathelicidin levels in non-diabetic, prediabetic and type II diabetic patients were measured by enzyme-linked immunosorbent assay.ResultsLentiviral cathelicidin overexpression reduced hepatic steatosis and decreased the fat mass of high-fat diet-treated diabetic mice. Cathelicidin overexpression reduced mesenteric fat and hepatic fatty acid translocase (CD36) expression that was reversed by lentiviral CD36 overexpression. Exposure of adipocytes and hepatocytes to cathelicidin significantly inhibited CD36 expression and reduced lipid accumulation. Serum cathelicidin protein levels were significantly increased in non-diabetic and prediabetic patients with obesity, compared with non-diabetic patients with normal body mass index (BMI) values. Prediabetic patients had lower serum cathelicidin protein levels than non-diabetic subjects.ConclusionsCathelicidin inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to a reduction of fat mass and hepatic steatosis in vivo. Circulating cathelicidin levels are associated with increased BMI. Our results demonstrate that cathelicidin modulates the development of obesity

Transdermal fluorescence detection of a dual fluorophore system for noninvasive point-of-care gastrointestinal permeability measurement

The intestinal mucosal barrier prevents macromolecules and pathogens from entering the circulatory stream. Tight junctions in this barrier are compromised in inflammatory bowel diseases, environmental enteropathy, and enteric dysfunction. Dual sugar absorption tests are a standard method for measuring gastrointestinal integrity, however, these are not clinically amenable. Herein, we report on a dual fluorophore system and fluorescence detection instrumentation for which gastrointestinal permeability is determined in a rat small bowel disease model from the longitudinal measured transdermal fluorescence of each fluorophore. This fluorophore technology enables a specimen-free, noninvasive, point-of-care gastrointestinal permeability measurement which should be translatable to human clinical studies

A potential role for muscle in glucose homeostasis: in vivo kinetic studies in glycogen storage disease type 1a and fructose-1,6-bisphosphatase deficiency

A potential role for muscle in glucose homeostasis was recently suggested based on characterization of extrahepatic and extrarenal glucose-6-phosphatase (glucose-6-phosphatase-beta). To study the role of extrahepatic tissue in glucose homeostasis during fasting glucose kinetics were studied in two patients with a deficient hepatic and renal glycogenolysis and/or gluconeogenesis. Endogenous glucose production (EGP), glycogenolysis (GGL), and gluconeogenesis (GNG) were quantified with stable isotopes in a patient with glycogen storage disease type 1a (GSD-1a) and a patient with fructose-1,6-bisphosphatase (FBPase) deficiency. The [6,6-H-2(2)]glucose dilution method in combination with the deuterated water method was used during individualized fasting tests. Both patients became hypoglycemic after 2.5 and 14.5 h fasting, respectively. At that time, the patient with GSD-1a had EGP 3.84 mu mol/kg per min (30% of normal EGP after an overnight fast), GGL 3.09 mu mol/kg per min, and GNG 0.75 mu mol/kg per min. The patient with FBPase deficiency had EGP 8.53 mu mol/kg per min (62% of normal EGP after an overnight fast), GGL 6.89 mu mol/kg per min GGL, and GNG 1.64 mu mol/kg per min. EGP was severely hampered in both patients, resulting in hypoglycemia. However, despite defective hepatic and renal GNG in both disorders and defective hepatic GGL in GSD-1a, both patients were still able to produce glucose via both pathways. As all necessary enzymes of these pathways have now been functionally detected in muscle, a contribution of muscle to EGP during fasting via both GGL as well as GNG is suggeste